PRESENTING PROBLEMS IN INFECTIOUS DISEASES

Fever• Documentation of fever: feeling hot or sweaty is not synonymous with fever Body temperature >38 ºC is a fever. • Axillary is less accurate than oral or rectal temp.

• Rigors. Shivering (followed by excessive sweating) implies a rapid rise in body temperature but rarely give a clue to etiology.

• Night sweats. These are characteristic of several infections (e.g TB, infective endocarditis).

• Excessive sweating without fever. Caused by Alcohol, anexiety, thyrotoxicosis, D.M, acromegaly,

lymphoma and excessive environmental heat

Accompanying features with fever:

• Headache. severe headache and photophobia, although characteristic of meningitis, may company other infections.

• Delirium. Mental confusion during fever is more common in young children or the elderly.

• Muscle pain. Myalgia may occur with viral infection, such as influenza, and with septicemia.

• Shock. Shock may accompany severe infections and sepsis.

HISTORY-TAKING IN FEBRILE PATIENTS

• Symptoms of common respiratory infections.• Genitourinary symptoms. Abdominal symptoms. • Joint symptoms. • Rash. • Travel history . • Drug history. Drug fever is uncommon and therefore

easily missed.• Alcohol consumption .

EXAMINATION OF THE FEBRILE PATIENT

Rash• Erythematous rashes (irregular erythematous patches that pale on

pressure and may be papular) Infectious causes include • human erythrovirus 19 infection • Measles, • scarlet fever• rubella may be non-infective, e.g. as a reaction to

medication.

A purpuric or petechial rash does not pale on pressureCaused by :• Meningococcal infection and meningococcemia• sepsis from any cause.• vasculitic lesions• thrombocytopenia• disseminated intravascular coagulopathy

Vesicular rashes may be caused by • chickenpox, shingles, • herpes simplex infection, • Coxsackie A virus infection (hand, foot and mouth

disease)

• Nodular skin lesions are caused by disseminated fungal infection and malignancy.

• Erythematous painful lesions on extensor surfaces of the limbs suggest erythema nodosum related to tuberculosis, sarcoid or drug reactions.

• Neck stiffness

• Cervical lymph nodes Enlargement of anterior and tonsillar nodes is

usually associated with tonsillitis or pharyngitis; posterior lymphadenopathy may suggest a glandular fever syndrome or HIV infection.

Mouth and oropharynx• Vesicular lesions, tonsillar exudates and palatal

petechiae suggest possible infectious aetiologies • Hairy leucoplakia of the tongue suggests HIV disease. • Oropharyngeal candidiasis may indicate immune

deficiency.

Eyes• Red eye suggests conjunctivitis, scleritis or uveitis.

• Conjunctival petechiae may be due to endocarditis.

• Proptosis may suggest thyroid eye disease. If it is unilateral, consider orbital infiltration by malignancy

or granulomatous disease.

PYREXIA OF UNKNOWN ORIGIN

DEFINITION 0f PUO

PUO is defined as a

• Fever higher than 38.0°C (101°F) on several occasions Persisting without diagnosis for more than 3 weeks without

diagnosis despite initial investigations for at least 3 outpatient visits or

3 days in the hospital without elucidation of a cause

AETIOLOGY OF PYREXIA OF UNKNOWN ORIGIN

1- Infections (30%):• Abscess at any site; • Imported infections, e.g. malaria, dengue, brucellosis • Enteric fevers .• Infective endocarditis. • Tuberculosis .• Viral infections • Fungal infections .

2- Malignancy (20%)• Hematological malignancies (Lymphoma, myeloma,

Leukaemias). • Solid tumors: bronchogenic ca. ca breast, hypernephroma,

retinoblastoma, ca pancreas 3- Connective t issue disorders (15%) • Vasculitic disorders .• Temporal arteritis /polymyalgia rheumatica .• SLE .• Still's disease .• Polymyositis .• Rheumatic fever.

AETIOLOGY OF PUO

AETIOLOGY OF PUO

4- Miscellaneous (20%) • Inflammatory bowel disease .• Liver disease. • Sarcoidosis. • Drug reactions. • Atrial myxoma .• Thyrotoxicosis .• Hypothalamic lesions. • Familial Mediterranean fever. 5- Idiopathic (15%)

Some important causes

• Extrapulmonary tuberculosis is the most frequent cause of FUO • Drug-induced hyperthermia, as sole symptom of an adverse

reaction to medication, should always be considered. • Disseminated granulomatoses such as Tuberculosis,

Histoplasmosis, Coccidioidomycosis, Blastomycosis and Sarcoidosis are associated with FUO.

• Lymphomas are the most common cause of FUO in adults• Thromboembolic disease (i.e. pulmonary embolism, deep venous

thrombosis) occasionally shows fever. • Although infrequent, its potentially lethal consequences warrant

evaluation of this cause.• Endocarditis, although uncommon, is another important etiology to

consider. • An underestimated reason is factitious fever. Patients frequently are

women that work, or have worked, in the medical field and have complex medical histories.[

EARLY TESTS IN THE INVESTIGATION OF PUO IN DEVELOPED COUNTRIES

• Full blood count (FBC) and differential .• ESR and CRP .• Serum ferritin. • Urea, creatinine and electrolytes .• Liver function tests (LFTs) and γ-glutamyl transferase. • Blood glucose .• Creatine phosphokinase (CPK).

Investigations (continue)

• Malaria blood films (if travel history). • Urinalysis . Midstream urine (MSU) for microscopy and

culture • Stool culture. • Sputum for routine microscopy and culture, and

microscopy for AFB and culture for mycobacteria .

• Blood cultures ×3 .• Chest X-ray .• Ultrasound examination of abdomen .• Electrocardiogram (ECG).

USEFUL SEROLOGICAL INVESTIGATIONS IN THE MANAGEMENT OF PUO IN DEVELOPED COUNTRIES

Viral:• CMV infection • Infectious mononucleosis • HIV infection • Hepatitis A, B and C infection • Erythrovirus infection

Bacterial : Lyme disease Chlamydial infection Brucellosis Mycoplasma infection Syphilis Leptospirosis

FURTHER NON-INVASIVE INVESTIGATIONS IN THE MANAGEMENT OF PUO

• Nucleic acid detection (polymerase chain reaction, PCR)

for tuberculosis, herpes simplex virus (HSV), CMV, HIV, erythrovirus, dengue, Toxoplasma, Whipple's disease

Immunological investigations• Autoantibody screen, including anti-double-stranded

DNA, anti-neutrophil cytoplasmic antibody (ANCA) • Immunoglobulins. • Complement (C3 and C4) levels. • Cryoglobulins.

Tuberculosis screening tests :

• Tuberculin (Mantoux) test. • Early morning specimen of urine (EMSU) ×3 for

mycobacterial microscopy and culture .

Imaging techniques

• Chest and abdominal X-rays may show lymphadenopathy or the absence of a psoas shadow.

• Ultrasound is rapid and non-invasive but often requires to be augmented by

• computed tomography (CT) or • magnetic resonance imaging (MRI) .

Imaging techniques

Chest and abdominal X-rays may show lymphadenopathy or the absence of a psoas

shadow.Ultrasound of abdomen • Liver tumour or metastases, liver abscess ,Dilated

intrahepatic bile ducts ,Renal tumour, abscess or hydronephrosis ,Ascites

Echocardiogram • Vegetations ,Atrial myxoma ,Intracardiac thrombus

CT/MRI of thorax and abdomen • Enlarged lymph nodes ,Organomegaly, Tumors and

abscesses, Lung and liver metastases .

Imaging techniques

Limited skeletal survey • Multiple myeloma ,• Bone metastases

Isotope bone scan • Malignancy ,• Osteomyelitis/septic arthritis

Labelled white cell scan • Abscesses/local sepsis,• Inflammatory bowel disease

The role of biopsies in investigation of PUO

Liver biopsy • Liver biopsy is a low-yield investigation which carries an estimated mortality

of approximately 0.01%. • The procedure may occasionally be required to diagnose tuberculosis,

lymphoma, or granulomatous disease including sarcoidosis.

Bone marrow biopsy • the diagnostic yield of a bone marrow biopsy in PUO is about 15%, • A biopsy is most useful in revealing haematological malignancy,

myelodysplasia and tuberculosis. • It may also lead to a diagnosis of brucellosis, enteric fever or visceral

leishmaniasis.

Temporal artery biopsy • should be considered in patients over the age of 50 complaining of

headache, joint pain, morning stiffness and high ESR possibility of crainial arteritis/ polymyelgia rheumatica

Up to one third of cases of PUO remain undiagnosed.

Therapeutic trials like

treatment of malaria, brucellosis, T.B. typhid fever

steroid for C.T. diseases

Factitious fever

• This is defined as fever, or the appearance of fever, that is engineered by the patient .

• This tends to be relatively more common in female patients and those with a medical or nursing background.

CLUES TO THE DIAGNOSIS OF FACTITIOUS FEVER

• A patient who looks well • Bizarre temperature chart with absence of diurnal

variation and/or temperature-related changes in pulse rate

• Temperature > 41°C • Absence of sweating during defervescence • Normal ESR and CRP despite high fever • Evidence of self-injection or self-harm • Useful methods for the detection of factitious fever

include supervised (observed) temperature measurement and measuring the temperature of freshly voided urine .

Prognosis in PUO

• The overall mortality of PUO is 30-40% • (5% in patients aged under 55 years, 40% in those age

over 55 years).

• Older patients are more likely to have a malignancy.

• If no cause is found on exhaustive investigation, the long-term mortality is low.

FEVER IN THE NEUTROPENIC PATIENT • Neutropenia is defined as a neutrophil count of less than

1.5 × 109/l.

• Patients with neutropenia, particularly less than 1.0 × 109/l, from either drug toxicity (including chemotherapy for cancer treatment), marrow invasion or failure, are particularly prone to bacterial infections.

• Gram-negative infections is the most common pathogens in this condition.

• It is both appropriate and potentially life-saving to start empirical broad-spectrum antibiotic therapy in these cases as soon as neutropenia is recognised and relevant specimens have been taken.